Drug Delivery Device

ABSTRACT

The present application provides a drug-delivery device comprising a drug reservoir chamber  16,  containing a substance to be delivered, in fluid connection with a drug administration means  18,  and an electrically-controlled battery unit  10  comprising at least one displacement-generating battery cell  19  coupled to the drug reservoir chamber  16  by a coupling means  14,  the arrangement being such that the displacement derived from the battery unit  10  is conveyed by the coupling means  14  to the drug reservoir chamber  16  such that the substance is expelled from the drug reservoir chamber  16  towards the drug administration means  18.

FIELD OF THE INVENTION

The present invention relates to the field of drug-delivery and relatesto a drug-delivery device driven by an electrically-controlleddisplacement-generating battery cell. More particularly, this inventionrelates to a displacement-generating battery cell which drives adrug-delivery mechanism, wherein the delivery rate can be very preciselycontrolled by an electrical circuit.

BACKGROUND OF THE INVENTION

In the field of battery cells, the volume change generated as thebattery charges or discharges is a known yet undesirable side effect,said effect being mentioned in the prior art. For example, US PatentApplication 20040115530 describes a method of preventing the detrimentaleffects of the volume change of the active material in a lead-acidbattery cell. In a co-pending patent application IL169,807 by some ofthe same inventors of this application, herein incorporated byreference, the concept of making use of such so-called “undesirable”volume changes in order to drive a drug-delivery device is described.However, said co-pending application exploits a relatively small volumechange (of the order of 10%) as known from traditional batterychemistries, and thus requires a hydraulic or other coupling mechanismin order to exploit the relatively small volume change in an effectivemanner.

Accordingly, the achievement of a novel battery cell capable of asignificant volume change (that is one capable of effectively driving adrug delivery device and herein referred to as a“displacement-generating battery”) allows for a unique, beneficial,simpler and therefore more inexpensive solution for drug-deliverydevices to be attained. Notably, such a drug-delivery device, in itssimplest embodiment, would not require any mechanical or hydraulicamplification and thus would represent an advance in the art, as itwould enable direct displacement of a drug in a reservoir within saiddrug-delivery device by said battery cell. In addition, since thedisplacement generated by said battery is directly related to theaccumulated electric discharge in the battery, the extent of thedisplacement of a drug in a reservoir can be very accurately controlled.

It is therefore the object of the present invention to provide adrug-delivery device driven by such a displacement-generating battery.

It is still further object of the present invention to provide adrug-delivery device whose delivery rate and volume of drug delivered isaccurately controlled by an electrochemical reaction, and specifically,by an electrochemical reaction that causes a volume change that actuatesthe delivery of the drug.

It is still further object of the present invention to provide adisplacement-generating battery that is used as an actuator whichtransmits a displacement resulting from an electrochemical reaction viaa coupling component in such a manner that a drug contained within adrug reservoir affected by the coupling is forced through anadministration means into the body of a patient.

It is a further object of the invention that said drug-delivery berelatively insensitive to temperature and ambient pressure changes.

It is a still further object of this invention to provide adrug-delivery device with a minimum of moving parts.

It is a still further object of this invention to provide adrug-delivery device where the displacement of the drug chamber can beinherently determined from the state of discharge of the battery.

It is a still further object of this invention to provide adrug-delivery device which does not suffer from a lag in response time.

It is a still further object of this invention to provide adrug-delivery device which is inherently waterproof.

It is still further object of the present invention to provide adrug-delivery device where control and maintenance issues are simplerthan in existing approaches and with less potential failure modes.

It is still further object of the present invention to provide adrug-delivery device in which the displacement-generating battery alsoprovides the power to operate the electronics of the device thusadvantageously obviating the need for having a further battery cell topower the electronics of the drug-delivery device and so the device issimplified, made more efficient, and lowered in cost.

These and other objects of this invention will become more evident inthe summary of the invention and in the description of the preferredembodiment.

SUMMARY OF THE INVENTION

According to the present invention there is now provided a drug-deliverydevice comprising a drug reservoir chamber, containing a substance to bedelivered, in fluid connection with a drug administration means, and anelectrically-controlled battery unit comprising at least onedisplacement-generating battery cell coupled to said drug reservoirchamber by a coupling means, the arrangement being such that thedisplacement derived from said battery unit is conveyed by said couplingmeans to said drug reservoir chamber such that said substance isexpelled from said drug reservoir chamber towards said drugadministration means.

In preferred embodiments of the present invention each of said at leastone displacement-generating battery cells comprises at least onevolume-changing element.

Preferably the volume of each of said at least onedisplacement-generating battery cells is changed as its respectiveelectrical capacity is changed.

In preferred embodiments of the present invention said coupling means ismechanical.

In some embodiments of the present invention said coupling meansinvolves a displaceable wall applying direct displacement from saidbattery unit to said drug chamber.

In especially preferred embodiments of the present invention saidcoupling means is a common wall of the battery cell and the drugreservoir.

In further preferred embodiments of the present invention, said couplingmeans involves a displaceable wall applying indirect displacement fromsaid battery unit to said drug chamber.

In a further preferred embodiment, said coupling means is hydraulic.

Thus according to a preferred embodiment of the present invention thereis provided a delivery device for drugs or other substances (herein a“drug-delivery device”) comprising a drug reservoir chamber having atleast one displaceable wall and containing a substance to be deliveredin fluid connection with a drug administration means, and adisplacement-generating element, said element being an electric batteryunit comprising at least one displacement generating battery cellscoupled to said drug chamber by a coupling means, the arrangement beingsuch that a change in the volume of at least one component of theelectrochemistry of said battery unit (during discharge or charge of thedisplacement-generating battery) causes a wall of the battery unit to bedisplaced, which in return causes a wall of said drug chamber to bedisplaced such that said substance is expelled from said drug chambertowards said drug administration means.

In preferred embodiments of the present invention said drugadministration means is selected from the group consisting of cannulas,cannula arrays, needle, micro-needle arrays, exit ports and transdermalpatches.

Said drug-delivery device may be employed in a number of differentconfigurations, including but not limited to: implantable devices,slow-infusion devices, disposable infusion devices, partially-disposableinfusion devices and patch-pumps attached to the skin. Such drugdelivery devices are useful for delivering drugs to patients which maybe humans or other animals. Given the absence of motors and other suchsensitive components, the drug-delivery device of the present inventionis inherently simple to render waterproof. The displacement-generatingbattery used in said device may be either a primary cell or a secondarycell, or involve more than one cell. Where a primary cell is used, thevolume change is caused by its discharge, and where a secondary cell isused, the volume change may be effected during either the charging ordischarging thereof. In either case, such a displacement-generatingbattery is hereby defined as one in which at least one component of thebattery cell undergoes a volume change of at least 20% or preferably atleast 30%, as opposed to conventional batteries which are designed sothat volume changes are minimized to substantially lower values. Thisvolume change is then conveyed, either directly or hydraulically, to adisplaceable wall of the drug chamber, causing the drug therein to bedelivered via the administration means.

The displaceable wall of the drug chamber can take a number of forms,including but not limited to: a rigid yet displaceable section of thewall, a flexible or bellows type wall section, a liquid-liquid interfaceand a piston. A simple example of a chamber with a displaceable wall isa cylindrical cell with a rigid circular cap sealed against one end bymeans of an elastomeric gasket, said cap being capable of moving up ordown as the charge/discharge proceeds. In all such cases, thedisplaceable section of the wall moves in response to the displacementof the wall of the displacement-generating battery. In the drug-deliverydevice of the present invention, said movement serves to expel a drugfrom a drug chamber in mechanical connection with said displaceablewall.

In a preferred embodiment of the present invention, thedisplacement-generating battery employed within the present inventionapplies direct displacement to a drug chamber wall, such that the drugcontained within said drug chamber is forced through an administrationmeans into the body of a patient. In a further preferred embodiment ofthe present invention, the displacement-generating battery appliesdirect force to a wall of a pouch or other envelope comprising the atleast partially flexible or displaceable walls of the drug chamber, suchthat the drug contained within said drug chamber is forced through anadministration means into the body of a patient. In a further preferredembodiment, the displacement-generating battery employed within thepresent invention pushes a piston of a drug chamber (either directly orvia mechanical or hydraulic coupling) such that the drug containedwithin said drug chamber is forced through an administration means intothe body of a patient. Said administration means can include aconventional cannula as known in the art, or any other means whereby thedrug is introduced into the body. Such means can include arrays of shortcannulas such as the SimpleChoice™ patch product (SpectRx, Inc.,Norcross, Ga., USA), arrays of micro-needles, non-invasive transdermaldevices, or auto needle insertion means. Alternatively, where thedrug-delivery device of the present invention is an implantable one, thedelivery means can be any exit port or tube leading from the device tothe required location in the body of the patient.

The key to this drug-delivery device is a battery cell, at least onecomponent of which undergoes a major volume change in excess of 20% andpreferably in excess of 30% of its initial volume, either during chargeor during discharge. In some cases, the overall change in volume of theentire battery is smaller than this amount (as one element shrinks or isdepleted while another grows), but this is not important providing thatit is still possible to mechanically exploit the volume-changingcomponent by mechanically supporting the displacement-generatingcomponent while ensuring that the cell casing as a whole does notcollapse or cause any other structural problem. In this manner, the fulldisplacement of the displacement-generating component—in this case anelectrode—may be exploited.

In general, such electrodes will benefit from a larger surface area,i.e. thinner sections and larger internal surface area, for examplethose achieved by using a pressed, pasted or sintered porous structureor one based on finer particles. This will allow easier access of ionsfor intercalation and enable higher rate discharges. In the case of adisplacement-generating battery, not only is the degree of expansionimportant, but also the force developed should be adequate fordrug-delivery. Internal stresses in the expanding electrode of at least1 kg/sq cm and preferably 10 kg/sq cm should be attainable in the courseof discharge or charge.

In especially preferred embodiments of the present invention at leastone displacement-generating battery cells employs a chemical reactionsystem based on electrochemical insertion of metal ions.

Preferably each of said at least one displacement-generating batterycells employs a chemical reaction system chosen from the group includingLi—Sn, (Li)LiC₆—Sn, Fe—LaNi₅, lithium-lead, lithium-antimony,lithium-silicon and lithium-bismuth.

Preferred electrochemical systems for said displacement-generatingbattery include but are not limited to Li—Sn and (Li)LiC₆—Sn; both ofwhich are based on the phenomenon of the increase of thickness (up to257%) of a tin (Sn) electrode under the chemical reaction with (orelectrochemical intercalation of) Li ions. A third system, Fe—LaNi₅(basically, a kind of a metal-hydride battery), could be used due to theexpansion of the Fe electrode (estimated as 250%) during its oxidationto FeOOH. Further candidates for anodes include alloys of lithium suchas (but not limited to) lithium-aluminum, lithium-magnesium,lithium-aluminum-magnesium, As will be obvious to one skilled in theart, various other displacement-generating battery chemistries can bechosen for the battery cell of this invention, subject only to thevolume-changing requirements discussed above. Further candidates forbattery systems include lithium-lead, lithium-antimony, lithium-silicon,lithium-bismuth and fuel cells; providing only that they achieve thevolume-changing requirements discussed above. In the case of fuel cellbatteries, the volume depletion of the fuel provides the volume-changingelement.

Lithium based batteries use organic solvents or a polymer electrolytetogether with a lithium ion-providing salt. Suitable non-limitingexamples of such organic solvents include propylene carbonate,tetrahydrofuran, 2-methyl tetrahydrofuran, gamma-butrolactone, ethylenecarbonate, dimethoxy ethane, dioxolane, diethyl carbonate, dimethylcarbonate, ethylmethyl carbonate, and various combinations of suchsolvents. Suitable non-limiting examples of electrolyte salts for suchorganic solvents include lithium perchlorate, lithiumhexafluoroaresenate, lithium hexafluorophosphae, lithiumtertrfluoroborate, LiCF₃SO₃, and LiN(CF₃SO₂)₂. In all these systems, asthe discharge or charge proceeds, there is either a net volume change ofthe system or a large volume change in at least one electrode.Variations on the above systems may use lithium-carbon, lithium-graphiteor lithium-aluminum alloys in place of the lithium electrode. An exampleof an electrolyte for the lithium-tin system is a solvent of a mixtureof ethylene carbonate and ethyl methyl carbonate with dissolved lithiumhexafluorophosphate as the ion-providing (ionizing) salt. Other lithiumion conducting electrolyte types are applicable, such as gel, polymer orsolid state electrolytes. The basic volume change in these systemsoccurs as a result of lithium ion intercalation from the lithiumelectrode into the other electrode during the electrochemical reaction,which is driven by the potential difference between the electrodes. Inthe case of a lithium-tin battery, the tin electrode can expand by up to257% in volume during discharge, while generating stresses of 15 kg/sqcm. This electrode expansion can be understood by comparing thedensities of lithium (0.53) and tin (7.3). Where the electrochemicalreaction within the displacement-generating battery is a reversible one,a battery cell of this type can also allow refilling of thedrug-delivery device.

This approach to drug-delivery device design has a number of advantages.As there is no pump or motor in the conventional sense, there are veryfew parts, and essentially only a coupling component such as adisplaceable wall between the cell and the drug chamber is a movingpart. By using a minimum number of moving parts, failure modes andmaintenance issues are minimized. Additionally, factors such as noise,friction, backlash and assembly tolerance issues are minimized.Accordingly, very precise control of the drug-delivery device is enabledby this design. In fact, providing that the non-displaceable walls ofthe battery remain rigid, the resolution of the achievable movement islimited only by the accuracy of the charge/discharge circuitry;something which can be provided to a very high degree using electroniccircuitry known in the art. This is especially important in the case ofimplantable drug-delivery devices, where drug-delivery rates in thepicoliter range per minute are required so as to be able to deliver drugquantities in the milliliter range over a period of months or years.Additionally, advantageously this approach provides the ability todetermine the volume of drug delivered, purely by integrating theelectric charge (that is, the current per unit time) used during chargeor discharge of the battery. Despite this, it should be apparent to oneskilled in the art that, where required, it is possible to furtherprovide (a) a closed-loop or feedback control where which incorporatesposition-detection elements such that the information concerning thevolume of drug delivered is not solely dependent on monitoring thecharge/discharge performed; and (b) pressure sensors and other feedbackand safety means can be incorporated into said control circuitry andlogic.

In preferred embodiments said drug-delivery device further comprises abattery recharging means. In said embodiments, said drug-delivery deviceis a multiple-use device.

In some embodiments of the present invention, said drug-delivery deviceis a patch-type pump.

In said embodiments said patch-type pump is preferably attached to thebody of a user by a means comprising an adhesion means, a strap, a claspand combinations thereof.

In other embodiments of the present invention, said drug-delivery devicefurther comprises auto-insertion means of the administration means.

In said other embodiments, said auto-insertion means preferably servesto insert the administration means.

In said other embodiments, said auto-insertion means preferablyautomatically activates the drug-delivery device.

In further preferred embodiments of the present invention saiddrug-delivery mechanism further comprises a plurality of drug chamberscontaining different drug components.

In said further preferred embodiments said drug-delivery devicepreferably includes means for the mixing of said different drugcomponents from said plurality of drug chambers.

In especially preferred embodiments of the present invention saiddrug-delivery device further comprises at least one battery cell.

Preferably said drug chamber includes means enabling the intake of bodyfluids; said fluids serving to dilute a drug for subsequentadministration by said drug-delivery device on reversion to its normaloperating mode.

In other embodiments of the present invention said device furthercomprises means for sampling body fluids for analysis.

In still further embodiments said drug-delivery device further comprisescommunications means to remote devices, said communications means beingselected from the group consisting of magnetic induction, infra-red, andRF devices.

In preferred embodiments of the present invention said administrationmeans further comprises a safety feature to protect against accidentalcontact or injury.

In especially preferred embodiments of the present invention, said drugreservoir chamber is coupled to said battery unit via a displaceablewall; such that the volume change from said battery unit serves tocontrol the rate of delivery of the drug.

In other preferred embodiments of the present invention said drugreservoir chamber is coupled to said battery via a piston arrangement;such that the volume change from said battery cell serves to control therate of delivery of the drug.

Preferably said at least one battery cell is a lithium-tin battery cellwhere the volume change in the tin electrode on discharge of said cellcauses the direct displacement of a displaceable wall of the drugchamber.

In preferred embodiments of the present invention the pressure in thedrug chamber is monitored as part of the control and safety logic of thesystem.

The invention will now be described in connection with certainnon-limitative preferred embodiments, with reference to the followingillustrative figures so that it may be more fully understood.

With specific reference now to the figures in detail, it is stressedthat the particulars shown are by way of example and for purposes ofillustrative discussion of the preferred embodiments of the presentinvention only and are presented in the cause of providing what isbelieved to be the most useful and readily understood description of theprinciples and conceptual aspects of the invention. In this regard, noattempt is made to show structural details of the invention in moredetail than is necessary for a fundamental understanding of theinvention, the description taken with the drawings making apparent tothose skilled in the art how the several forms of the invention may beembodied in practice.

Additional objects and advantages of the invention are set forth herein,or will be apparent to those of ordinary skill in the art from, thedetailed description as follows. Also, it should be further appreciatedthat modifications and variations to the specifically illustrated anddiscussed features and materials hereof may be practiced in variousembodiments and uses of this invention without departing from the spiritand scope thereof, by virtue of present reference thereto. Suchvariations may include, but are not limited to, substitutions of theequivalent steps, means, features, and materials for those shown ordiscussed, and the functional or positional reversal of various steps,parts, features, or the like.

Still further, it is to be understood that different embodiments, aswell as different presently preferred embodiments, of this invention,may include various combinations or configurations of presentlydisclosed steps, features, elements, or their equivalents (includingcombinations of steps, features or configurations thereof not expresslyshown in the figures or stated in the detailed description).

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings, wherein:

FIG. 1 provides a block diagram of the overall drug-delivery device,showing its main components;

FIG. 2 provides cross-sectional and isometric views of a preferredembodiment of the drug-delivery device with a displaceable wall betweenthe battery cell and the drug chamber;

FIG. 3 provides cross-sectional and isometric views of a preferredembodiment of a battery cell for use within the present invention;

FIG. 4 provides cross-sectional and isometric views showing theintegration of a number of different administration means into thedrug-delivery device; and

FIG. 5 shows isometric and cross-sectional views of additional preferredembodiments of the drug-delivery device, including one in the form of apen and one in which there is hydraulic coupling between the batterycell and the drug chamber.

DETAILED DESCRIPTION OF THE DRAWINGS

The present invention will be described in detail according to thepreferred embodiments illustrated in the accompanying drawings. Likereference numerals are used to identify identical components in thevarious views.

Referring to FIG. 1 a, a simplified block diagram of the drug-deliverydevice of the present invention is shown so as to illustrate the maincomponents involved. In this illustrative embodiment, a battery cell 10is shown adjacent to a drug chamber 16 with a displaceable wall 14between them, such that expansion of the volume-changing component 19 ofthe battery 10 causes said displaceable wall 14 to decrease the volumeof the drug chamber 16. The battery 10 is activated and controlled bythe control circuit 12; the activation of said battery 10 causing itsvolume-changing component 19 to expand in this example. Said expansioncauses the drug chamber 16 to contract such that the drug is expelledthrough the drug administration means 18. In a preferred embodiment,said expulsion takes place via a valve 15 leading to drug administrationmeans 18. Referring now to FIG. 1 b, the situation after the battery 10has been activated is shown, illustrating the significant change involume of its volume-changing component 19. Note that, depending on thebattery chemistry, the electric circuit will either discharge thebattery 10 in order to cause the volume change, or charge the battery inorder to achieve this change. For this reason both a battery and aresistor are shown within the block diagram of said circuit 12 for aschematic representation of its functionality. If the depletion methodis used, advantageously this obviates the need for having a furtherbattery cell to power the drug-delivery device of the present inventionas the device is thereby self-powered to some extent, further reducingcosts. Note also that the volume-changing component 19 of the batterycell 10 does not have to be an expanding component as shown but could,by a slightly different mechanical arrangement be a contractingcomponent.

Referring now to FIG. 2, a cross-sectional view of a preferredembodiment of the drug-delivery device of the present invention isprovided. FIG. 2 a shows the configuration prior to activating thebattery, while FIG. 2 b shows the configuration of this device at theend of the device's operation. This embodiment comprises a housing 20which contains the battery 10 and a drug chamber 16. In this embodiment,the expansion of the battery 10 moves a coupling means 25 in a shape ofa plate which in turn displaces the displaceable wall 14 and reduces thevolume of the drug chamber 16, causing the drug to be expelled via theadministration means 18. In the preferred embodiment shown, said plate25 is covered by a displaceable wall 14 of the drug chamber 16, saiddisplaceable wall 14 incorporating a bellows-shaped circumference. Inthis preferred embodiment, the use of the displaceable wall 14 in thismanner enables the optimal use of the drug chamber 16 shape in that saidchamber 16 can be almost completely depleted by the displacement of saidplate 25. Additionally, the bellows section of this displaceable wall 14provides a counter-force to the force generated by the cell 10, ensuringthat the displacement produced operates in a controlled fashion and isless susceptible to motion artifacts. As will be obvious to one skilledin the art, such a counter-pressure effect can alternatively beperformed by the use of any other counter pressure means including butnot limited to springs, or other compressible elements. The volumechange under the displaceable wall 14 will be compensated either byhaving an opening (not shown) to the ambient air through the bottom sideof the housing 20 or by using any other volume compensation means knownin the art. An electronic control unit 12, which controls the dischargeof the battery 10 is further incorporated in the drug-delivery device.Said control unit 12 may be interfaced with a pressure sensor (notshown) located either within the drug chamber 16, on the walls of thedrug chamber 16, or along the liquid path to the administration means18, in order to serve as the occlusion detector and send a signal backto the control unit 12 to stop the activation of the battery 10. As willbe obvious to one skilled in the art, a suitable wiring arrangement (notshown) whereby both polarities of the cell 10 are connected to contactsattached to said control unit 12 is provided. Suitable materials for thehousing 20 include plastics including but not limited to polyethylene(PE) and polypropylene (PP), or metal such as stainless steel; andsuitable materials for the displaceable wall 14 include stainless steel,aluminum, rigid plastics or multilayer films.

Advantageously, this embodiment uses a small, lightweight battery 10which has a small diameter relative to the diameter of the housing 20;such that the resulting device is light relative to the volume of drugit can deliver. For example the diameter of the battery 10 can be 10-30mm, while the diameter of the drug chamber 16 is 20-60 mmcorrespondingly. Thus an amplification effect is achieved whereby arelatively narrow piston presses upon a drug chamber of broaderproportions. Note that this does require relatively high force to begenerated by the battery cell 10, but the cells described in thepreferred embodiment below successfully generate this force.

Referring now to FIG. 2 c, an isometric view of the drug-delivery deviceof the present invention is provided, showing the housing 20, anelectronic control unit 12 inserted into a recess in said housing and adelivery means 18 shown here as a thin tube. The housing 20 furthercomprises an air-evacuation channel (not shown) for the evacuation ofair from said recess as said control unit 12 is inserted. Said controlunit 12 may be a disposable, semi-disposable or permanent one. Where itis either semi-disposable or permanent, it may interlock with a locationon the drug-delivery device (for example as shown in the presentembodiment) so as to enable easy insertion and removal. Advantageously,making this control unit 12 re-usable reduces the cost of using thedrug-delivery devices of the present invention, as then the cost of onecontrol unit 12 may be spread over the use of many disposable devices.In a preferred embodiment, said battery cell 10 is simply discharged (ina controlled manner) by said control unit 12, making the device of thepresent invention essentially self-powered. Some examples of differentdelivery means suitable for use with this device are provided within thecontext of FIG. 4 below. The design can be either a circular one asshown, or a square design can be used. The unexploited space in thisembodiment can, advantageously, be used for the electrical componentssuch as sensors, buttons and/or a buzzer (all not shown). As will beobvious to one skilled in the art, in a preferred embodiment, all theelements of the drug-delivery device and its internal wiring areprotected against environmental influences such as humidity.

It will be obvious to one skilled in the art that the drug does not haveto be in direct contract with the displaceable wall 14 and the innersurface of the housing 20, but rather can be maintained within aflexible pouch. Suitable materials for fabricating such a drug pouchinclude but are not limited to high-density polyethylene (HDPE) andpolypropylene (PP) or any type of multi-layer film including suchmaterials. From a regulatory perspective, this embodiment isadvantageous as it enables the drug-filling to be performed in aseparately controlled and regulated fabrication environment, while theintegration of the pouch into the complete drug-delivery device canpotentially be performed in a less controlled environment.

Referring now to FIG. 3, a preferred embodiment of the battery cell 10which drives the drug-delivery device is shown. In a preferredembodiment, the lithium-tin battery chemistry is employed. FIG. 3 aprovides a cross-sectional view of said cell showing its internalstructure, while FIG. 3 b provides a isometric view showing theconcertina-like structure formed; both showing the initial state of thecell 10 before activation. As shown in FIG. 3 a, said cell 10 comprisesa flexible metal sheet housing 35 formed according to aconcertina-shaped design; said housing 35 containing a lithium cathode30 and a tin anode 19 which, in this embodiment, is the expandingelement. The cell 10 further comprises a rigid cylindrical metallic mesh33 which surrounds the tin anode 19; there being also a separator (notshown) between the lithium cathode 30 and said mesh 33. Thus thearrangement of the battery components is a concentric cylinder one,where all the remaining volume within the cell 10 is taken up by theelectrolyte 32. In this preferred embodiment, the electrolyte 32 usedfor the lithium-tin system is a solvent of a mixture of ethylenecarbonate and ethyl methyl carbonate with dissolved lithiumhexafluorophosphate as the ion-providing (ionizing) salt. As the cell 10is depleted, the lithium ions penetrate the tin cathode 19 causing it toexpand. In the present embodiment, said expansion is constrained to takeplace primarily in the vertical direction due to the rigidity of themesh 33 which prevents expansion to the sides. Said expansion thereforetakes place against the rigid battery cap 37. In this embodiment the cap37 serves as one pole of the battery and the housing 35 serves as thesecond pole. The sealing between the cap 37 and the housing 35 iselectrically insulated. The wiring from the control unit will beconnected to these battery poles. The housing 35 can be made frommaterials other than metal such as multilayer films as described inpatents U.S. Pat. Nos. 5,134,046, and 6,296,967) which arenon-conductive, and the wiring arrangement can be as known in the art,for example as per U.S. Pat. No. 6,296,967.

Referring now to FIGS. 3 c and 3 d, the state of the battery cell 10 asit is fully depleted is shown, in cross-sectional and isometric viewsrespectively. Full depletion means that all the lithium ions havemigrated into the tin cathode 19, leaving only electrolyte 32 behind.The resulting expansion of the cathode 19 has raised the position of thebattery cap 37, causing an overall change in the shape of the cell. Saidchange is enabled by the flexible nature of the cell's housing 35. Inthe preferred embodiment shown, the flexible concertina shape shown isreadily adaptable to the new configuration of the battery cell 10, as itadjusts to being lengthened by reducing the extent of the folds in theside walls and at the same time moving inwards in order to adapting tothe overall volume change in the cell In this manner, the cell 10becomes taller but narrower to reflect the expansion of itsvolume-changing component.

Note that in this preferred embodiment, the tin cathode 19 needs to behighly porous while also preserving mechanical strength. In a preferredembodiment it is prepared by making a 2:1 mixture (by volume) of Snpowder and a powder of table salt, NaCl. This mixture was pressurized ina stainless steel mold under 5 tons of pressure to form theappropriately sized pellet. This pellet was then boiled several times indistilled water, with fresh portions of distilled water being used eachtime, and then, finally, sonicated in distilled water for 5 minutes.After drying and weighing the pellet, full dissolution of the NaCl wasverified. In this way, highly dispersed and highly porous, yetmechanically stable Sn electrodes were prepared. The constraining of theSn pellet as it expands was solved by designing a stainless steel meshcylinder as a holder for this pellet. The porosity enables the lithiumions to penetrate the tin (via the electrolyte), while the mesh controlsthe direction of said expansion. Note also that in this embodiment, asthe Li is consumed, it is important to concentrate the remaining Liclose to this mesh, and thus a copper (Cu) net cylinder (not shown)surrounds the lithium for this purpose.

As will be obvious to one skilled in the art, a number of differentembodiments of the battery cell 10 could be applied in the design of thecell. For example, the anode 19 need not be constrained to only expandupwards, but could alternatively be constrained to expand downwards, orbe allowed to expand in both directions simultaneously. Note that in thepreferred embodiment shown, the lithium anode 30 extends higher than thetin cathode 19 so as to maximize the adjacent surface between the two,in order to enhance the ion transport. However, in order to produce alower profile cell, an embodiment in which the initial height of bothelectrodes is close to identical may be used. In this embodiment, theion transport is less efficient as the tin cathode 19 expands and theprotruding part of it is no longer adjacent to the lithium anode 30, butthis lack of chemical efficiency is a trade-off that may be worth makingin order to enable the drug-delivery device to be miniaturized moreeffectively. In a further preferred embodiment, the arrangement ofcathode and anode may be one employing parallel layers, one above theother; in or similar to the manner of a button cell. In a furtherpreferred embodiment, a multiplicity of anodes and cathodes may be usedto produce the desired displacement.

In a further embodiment the construction of the battery cell is on aPrinted Circuit Board (PCB): the electrodes will be selectively“printed” on the circuit board in contact with conductive channels. Thearea of the electrodes will be confined under a flexible first coversealed to the PCB and filled with electrolyte, said first cover beingthe displaceable wall of the battery. In a preferred embodiment a coveris placed around said first cover and sealed against the PCB, formingthe drug chamber. It is obvious to those skilled in the art that anyfashion of coupling means can be introduced between the displaceablewall of the battery and the displaceable wall of the drug chamber. Thecontrol circuit can be placed on the same PCB helping to furtherminiaturize the assembly and increase reliability. This embodiment isadvantageous for small drug chamber applications where compactization iscrucial such as implantable controlled drug release devices.

Referring now to FIG. 4, a number of alternative types of administrationmeans 18 are shown. The administration means 18 can take numerous formsdepending on the type of application for which the drug-delivery deviceof the present invention is being used. As will be clear to one skilledin the art, the administration means 18 can be any means whereby thedrug or other substance delivered by the device enters the patient'sbody, including but not limited to an exit port in an implantableversion of the device, and a cannula, cannula array or transdermal patchfor an external device. In its simplest form said administration meansis simply a conduit extending from the device. Referring now to FIG. 4a, said conduit 50 leads to a Luer lock, which is a standard connectorto an infusion set. Alternatively, and as shown in FIG. 4 b, the Luerlock is incorporated into the housing 20 of the device. In the furtherpreferred embodiment shown in FIG. 4 c, an isometric view of anembodiment in which the administration means 18 is a cannula is shown.Said cannula is in fluid connection with the drug chamber 16, andextends either directly from the housing 20, or from a tab projectingtherefrom (not shown). Said cannula may be a rigid one or an array ofsmall rigid ones. In a further preferred embodiment, a flexible cannulasuch as the Teflon® type cannulas known in the art may be used. In thelatter case, said cannula can be inserted into the patient's body bymeans of an insertion device. In a still further preferred embodiment,the cannula can be inserted into the body by a mechanism internal to thedrug-delivery device of the present invention.

Referring now to FIG. 4 d, a side view of a further preferred embodimentis provided. In this embodiment, the administration means 18 is an arrayof mini or micro-needles extending from the base of the housing 20 ofthe device. This embodiment is especially suitable for a low-profileversion of the device, where only a small drug volume is required.Examples of micro-needle arrays include the Microstructured TransdermalSystems (MTS) array from 3M Drug-delivery Systems (St. Paul, Minn.,USA). Advantageously, this type of array enables the disruption of theoutermost layer of the skin, the stratum corneum, without causing pain;and thus the drug device of the present invention which integrates suchan array can be applied to the skin in a completely painless manner.

In general the drug-delivery device of the present invention is suitablefor use as a patch-pump for delivering drug volumes between 0.5 mL and10 mL. Embodiments at the lower end of this range will be more coin-likein shape, whereas those at the higher end will be more reminiscent ofthe embodiments shown in FIGS. 2 and 4. A patch-pump of this nature canbe applied to the skin in a number of manners, including but not limitedto the use of adhesives, straps and such-like. It may also be desirableto automatically activate the drug-delivery device when theadministration means 18 is applied to the skin, or when anauto-insertion means of a cannula is activated.

Referring now to FIGS. 5 a and 5 b, isometric and cross-sectional views(respectively) are shown of a pen-shaped preferred embodiment of thedrug-delivery device of the present invention. In this preferredembodiment, a multiplicity of battery cells 10 as described above arearranged in series such that their combined displacement presses upon adisplaceable wall 14. Said displaceable wall 14 acts as a piston withinthe drug chamber 16; the movement of said piston 14 serving to expel thedrug. In a preferred embodiment of this configuration, the pen-shape isterminated at its upper end with a Luer lock serving as theadministration means 18, and the electronic control unit 12 isintegrated into the pen's base. This embodiment has the advantage ofefficiently exploiting the available volume, such that there is littleof no “dead space” within the device's housing. Additionally, the penform-factor is well known, easy to clip on to shirt or jacket andunobtrusive; while also obviating the need to adhere the device to theskin. As will be obvious to one skilled in the art, the relativelocation of the components within the pen shape can easily be altered,and thus if it is preferred to have the Luer lock on the bottom and theelectronics at the top, this is trivial to achieve.

A further advantage of this embodiment is that the shape of the drugchamber 16 enables a vial with an integral piston to be used. This useof such a vial is further described in connection with FIGS. 5 c, 5 dand 5 e, in which hydraulic coupling is utilized to couple the batterycell 10 to a vial 55. This embodiment enjoys the advantage that it mayuse relatively standard vials, which are typically made from glass andcan hold a drug for an extended period. Such a vial 55 may be insertedinto the device shown by the user, thereby reducing regulatoryrequirements in the development of such a device. In this preferredembodiment, the expansion of the volume-changing component of the cell10 causes the contraction of a reservoir 57 containing hydraulic fluid.On said contraction, said hydraulic fluid is expelled via hydraulicconduit 56 where it presses upon a piston (not shown) at the base ofsaid vial 55; thereby causing the drug contained within said vial 55 tobe expelled. It will be clear to one skilled in the art that thecoupling between the battery cell 10 and the vial 55 may be achieved viaany coupling means including but not limited to mechanical barmechanisms, mechanical trains, pulleys, etc., resulting in eitherproportional motion or a more complex exponential correlation.

It will be noted that while all the above embodiments employ anexpanding element within the battery cell, it will be clear to oneskilled in the art that the drug-delivery device could equally well bedriven by a contracting element within said cell, by changing themechanical operation. Examples of this approach are shown in co-pendingapplication IL169,807. Additionally, springs may advantageously beincorporated into the device in a number of configurations. For example,all the embodiments described above will achieve greater stability byhaving the driving force partially counterbalanced by an opposingspring. This will ensure smoother movement and provide greater artifactresistance. In a further preferred embodiment, the spring can providethe driving force while the cell serves as a brake. The advantages ofthis approach and further details of its implementation are described inco-pending published application WO2004067066 by one of the sameauthors; hereby incorporated by reference. It will also be obvious toone skilled in the art that the connection between the battery cell andthe drug chamber can be any kind of mechanical, hydraulic, magnetic orother coupling means known in the art; and that said coupling action mayresult in either a proportional or an exponential correlation between amultiplicity of such drug chambers and a multiplicity of such cells.Note that in certain systems according to this embodiment the drivingforce will be the combination of the force exerted by the spring and thecontraction/expansion of the cell.

Whereas the embodiments above describe relatively simple configurationsof the drug-delivery device of the present invention, the generalprinciples involved in said invention enable the implementation of alarge number of further embodiments; said further embodiments addressingfurther issues in such devices, such as refilling, drug dilution,delivery of a multiplicity of drugs (with or without mixing) and thefabrication of sophisticated implantable versions. For example, acombination of two cells driving in opposite direction may be employedin order to enable two-way motion of a drug chamber piston in order toallow refilling of the drug chamber. Similarly, if it is desired toprovide an implantable drug-delivery device which is able to work overan extended period, a second drug chamber containing ahighly-concentrated form of the drug to be delivered can beincorporated. In a preferred embodiment, a small amount of said drugconcentrate from the second or reservoir chamber is introduced to thedrug chamber while body fluids are also introduced into said drugchamber to dilute it. In this way, further described in co-pendingpatent application IL169,807, the drug chamber is re-filled using aconcentrate and then may resume its slow-infusion mode of operation. Aswill be obvious to one skilled in the art, the concentrated drug can bein either liquid or solid form, and the mechanism as described above canprovide drug-delivery over an extended period without requiring externalrefilling. Likewise, the ability to use the drug-delivery device of thepresent invention to perform intake of body fluids enables said deviceto further incorporate various body fluid sampling and/or analysiselements.

In another preferred embodiment, the drug delivery device is driven by adisplacement-generating battery, such battery increasing its volume dueto an electrochemical reaction that discharges the battery; where suchvolume expansion actuates a coupling device to expel a drug from thedrug chamber via an administration means to the patient.

In yet another preferred embodiment, the drug delivery device is drivenby a displacement-generating battery containing an expanding electrodewhich expands due to cell discharge and whose volume expansion can beexploited to actuate a coupling device to expel a drug from the drugchamber via an administration means to the patient.

Regarding the electrical or electronic control circuit of thedrug-delivery device of the present invention, it will be apparent tothose skilled in the art that a wide range of electronic control systems(not shown) may be incorporated within (or interfaced to) said device.Said range includes: (a) microprocessor-controlled variable-resistanceor load elements for controlled discharge of the cell; (b) removablecontrol units that enable a semi-disposable device to be constructedwhereby all or part of the control circuitry may be moved fromdisposable section to disposable section; (c) systems comprising aremote-control element; (d) systems that interface to a flow-controlfeedback element monitoring the actual drug-delivery rate, eitherdirectly or indirectly; (e) an interface control unit that receivessignals related to medical parameters such as blood-glucose levels,other blood-analyte levels and body temperature; and (f) any combinationof the above. Advantageously, said electronics circuit and/or electroniccontrol systems may be at least partially powered by the very depletionof power that drives the drug-delivery device, thereby in many casesobviating the need to provide a battery to power the electronics of sucha device. Additionally, in the case of an implanted device, the designmay further employ embedded electronics sealed by resin casting or othersealing means known in the art, and various communication meansincluding but not limited to magnetic coupling transmission, RF or IRtransmission.

Preferred chemical systems for the battery cell of the drug-deliverydevice of the present invention are those which are non-gassing or inwhich there is minimal parasitic gas production. Nevertheless, in thecase that the selected chemical reaction does generate gas and themechanical embodiment is sensitive to gas (note that the embodimentswith high counter force are less sensitive to gas) said gas may eitherbe vented via a gas-permeable membrane or recombined via a catalyticplug such as those made by Hoppecke Battery Company, Germany. As allcell walls other than the displaceable one must remain fixed and rigidin order to maintain the accuracy of the slow-infusion device, it isimportant that such membrane be provided with an appropriate supportstructure so as not to detract from the rigid structure of the cell.These gas eliminating means are arranged in a fashion that efficientlyoperates in every operational orientation of the device. Suitablegas-permeable membranes include Fluoropore™ membrane from Millipore Inc.(Billerica, Mass., USA) and Emflon™ from Pall Inc. (East Hills, N.Y.,USA).

While the invention has been shown herein in what is presently conceivedto be the most practical and preferred embodiment thereof, it will beapparent to those of ordinary skill in the art that many modificationsmay be made thereof within the scope of the invention, which scope is tobe accorded the broadest interpretation of the appended claims so as toencompass all equivalent structures and devices.

1. A drug-delivery device comprising a drug reservoir chamber,containing a substance to be delivered, in fluid connection with a drugadministration means, and an electrically-controlled battery unitcomprising at least one displacement-generating battery cell coupled tosaid drug reservoir chamber by a coupling means, the arrangement beingsuch that the displacement derived from said battery unit is conveyed bysaid coupling means to said drug reservoir chamber such that saidsubstance is expelled from said drug reservoir chamber towards said drugadministration means.
 2. A drug-delivery device according to claim 1wherein said drug administration means is selected from the groupconsisting of cannulas, cannula arrays, needle, micro-needle arrays,exit ports and transdermal patches.
 3. A drug-delivery device accordingto claim 1 wherein each of said at least one displacement-generatingbattery cells comprises at least one volume-changing element.
 4. Adrug-delivery device according to claim 1 wherein the volume of each ofsaid at least one displacement-generating battery cells is changed asits respective electrical capacity is changed.
 5. A drug-delivery deviceaccording to claim 3 wherein each of said at least onedisplacement-generating battery cells employs a chemical reaction systembased on electrochemical insertion of metal ions.
 6. A drug-deliverydevice according to claim 5 wherein each of said at least onedisplacement-generating battery cells employs a chemical reaction systemchosen from the group including Li—Sn, (Li)LiC₆—Sn, Fe—LaNis,lithium-lead, lithium-antimony, lithium-silicon and lithium-bismuth. 7.A drug-delivery device according to claim 1 wherein said battery unitserves to power at least some of the electrical and electronic elementsof said device.
 8. A drug-delivery device according to claim 1 wheresaid coupling means is mechanical.
 9. A drug-delivery device accordingto claim 8 where said coupling means involves a displaceable wallapplying direct displacement from said battery unit to said drugchamber.
 10. A drug delivery device according to claim 9 where saidcoupling means is a common wall of the battery cell and the drugreservoir.
 11. A drug-delivery device according to claim 8 where saidcoupling means involves a displaceable wall applying indirectdisplacement from said battery unit to said drug chamber.
 12. Adrug-delivery device according to claim 1 where said coupling means ishydraulic.
 13. A drug-delivery device according to claim 1 wherein saiddrug-delivery device is disposable.
 14. A drug-delivery device accordingto claim 1 wherein some parts of the said drug-delivery device aredisposable.
 15. A drug-delivery device according to claim 1 wherein saiddrug-delivery device is an implantable device.
 16. A drug-deliverydevice according to claim 1 wherein said drug-delivery device furthercomprises a filling means.
 17. A drug-delivery device according to claim1 wherein said drug-delivery device further comprises a batteryrecharging means.
 18. A drug-delivery device according to claim 1wherein said drug-delivery device is a multiple-use device-.
 19. Adrug-delivery device according to claim 1 wherein said drug-deliverydevice is a patch-type pump.
 20. A drug-delivery device according toclaim 19 wherein said patch-type pump is attached to the body of a userby a means comprising an adhesion means, a strap, a clasp andcombinations thereof.
 21. A drug-delivery device according to claim 1wherein said drug-delivery device further comprises auto-insertion meansof the administration means.
 22. A drug-delivery device according toclaim 21 wherein said auto-insertion means serves to insert theadministration means.
 23. A drug-delivery device according to claim 21wherein said auto-insertion means automatically activates thedrug-delivery device.
 24. A drug-delivery device according to claim 1wherein said drug-delivery mechanism further comprises a plurality ofdrug chambers containing different drug components.
 25. A drug-deliverydevice according to claim 24 wherein said drug-delivery device includesmeans for the mixing of said different drug components from saidplurality of drug chambers.
 26. A drug-delivery device according toclaim 1 wherein said drug-delivery device further comprises a pluralityof battery cells.
 27. A drug-delivery device according to claim 15wherein said drug chamber includes means enabling the intake of bodyfluids; said fluids serving to dilute a drug for subsequentadministration by said drug-delivery device on reversion to its normaloperating mode.
 28. A drug-delivery device according to claim 27 whereinsaid device further comprises means for sampling body fluids foranalysis.
 29. A drug-delivery device according to claim 1 wherein saiddrug-delivery device further comprises communications means to remotedevices, said communications means being selected from the groupconsisting of magnetic induction, infra-red, and RF devices.
 30. Adrug-delivery device according to claim 2 wherein said administrationmeans further comprises a safety feature to protect against accidentalcontact or injury.
 31. A drug-delivery device according to claim 1,wherein said drug reservoir chamber is coupled to said battery unit viaa displaceable wall; such that the volume change from said battery unitserves to control the rate of delivery of the drug.
 32. A drug-deliverydevice according to claim 1, wherein said drug reservoir chamber iscoupled to said battery via a piston arrangement; such that the volumechange from said battery cell serves to control the rate of delivery ofthe drug.
 33. A drug-delivery device according to claim 1 wherein saidbattery cell is a lithium-tin battery cell where the volume change inthe tin electrode on discharge of said cell causes the directdisplacement of a displaceable wall of the drug chamber.
 34. A drugdelivery device according to claim 1 where the pressure in the drugchamber is monitored as part of the control and safety logic of thesystem.
 35. A drug delivery device according to claim 1 wherein saiddevice is selected from the group consisting of implantable devices,slow-infusion devices, disposable infusion devices, partially-disposableinfusion devices and patchpumps attached to the skin.
 36. A drugdelivery device according to claim 1 wherein said displacementgenerating battery is a primary cell.
 37. A drug delivery deviceaccording to claim 1 wherein said displacement generating battery is asecondary cell.
 38. A drug delivery device according to claim 1 whereinat least one component of the battery unit undergoes a volume change ofat least 200/0.
 39. A drug delivery device according to claim 1 whereinat least one component of the battery unit undergoes a volume change ofat least 30%.
 40. A drug delivery device according to claim 1 whereinsaid drug chamber is provided with a rigid displaceable wall section.41. A drug delivery device according to claim 1 wherein said drugchamber is provided with a flexible displaceable wall section.
 42. Adrug delivery device according to claim 1 wherein the displacementderived from said battery unit exerts a force of at least 1 kg/sq.
 43. Adrug delivery device according to claim 1 wherein the displacementderived from said battery unit exerts a force of at least 10 kg/sq. 44.A displacement-generating battery cell for driving a drug-deliverydevice and comprising at least one volume-changing element, said cellcomprising a housing formed according to a concertina-shaped design withfolds in the walls thereof and containing an internal chemical reactionsystem, the arrangement of said chemical reaction system being such thatas the cell is discharged, said volume-changing element expands, therebylengthening the battery and thus reducing the extent of said folds, suchthat the cell becomes taller to reflect the expansion of saidvolume-changing component.